Developmental studies for AIDS vaccines have focussed on vectored approaches. Chimpanzees primed with adenovirus human immunodeficiency virus type 1 (HIV-1) (MN) recombinants and boosted with HIV-1 (SF2) envelope were challenged with the SF2 isolate. While a mock-immunized chimpanzee quickly became infected, 3 chimpanzees with neutralizing antibodies were protected from SF2 infection. Another chimpanzee which developed a cytotoxic T-lymphocyte response but no neutralizing antibody was also protected, suggesting a role for cell-mediated immunity in vaccine protection. Evaluation of a higher dose challenge is ongoing. Studies using adenovirus host range mutant-simian immunodeficiency virus recombinants are aimed at evaluating a mucosal challenge in rhesus macaques. Previously, immunization of rhesus macaques with attenuated poxvirus HIV-2 recombinants has been shown to elicit long-lasting protection against an HIV-2 challenge. In addition, immunization with attenuated poxvirus HIV-1 recombinants caused cross-protection against an HIV-2 challenge. A recent study suggests that a long immunization schedule is necessary for development of protective immunity. Ongoing studies using larger numbers of animals are investigating immune responses associated with protection, especially aspects of cell-mediated immunity, the role of a CD8+ cell suppressor factor, and neutralization of primary isolates in peripheral blood lymphocytes and macrophages. In humans, immune correlates of protection are being studied in discordant couples and in children who are fast or slow progressors. Biologic and molecular analyses of HIV-1 escape mutants, designed to identify structurally and functionally important regions of the viral envelope, continue to pinpoint the CD4 binding region as critical for numerous virus-host interactions. Studies modeling the CD4 binding region have identified conformationally constrained peptides which functionally and antigenically mimic the CD4 region of gp120. Finally, molecular epidemiologic studies have identified several HIV-1 subtypes in the highly populous African nation of Nigeria. This information will be useful in development of vaccines targeted to particular geographic regions as well as in design of globally effective vaccines.